A Phase 2/3, Randomized, Placebo-Controlled, Double-Blind Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MK-4482 in Hospitalized Adults With COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 304
- 试验地点
- 89
- 主要终点
- Time-to-sustained Recovery
研究概览
简要总结
This study aims to evaluate the safety, tolerability and efficacy of molnupiravir (MK-4482) compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as assessed by the rate of sustained recovery through Day 29.
详细描述
This study was intended to include two parts: Part 1 was a dose-ranging phase 2 study, and Part 2 was a phase 3 study to evaluate the dose selected in Part 1. However, this study was terminated due to business reasons prior to conducting Part 2. Participants in Part 1 were followed until Month 7.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has documentation of polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with sample collection ≤ 10 days prior to the day of randomization. PCR is the preferred method; however other diagnostic methods are allowed if authorized by use in the country
- •Had initial onset of signs/symptoms attributable to COVID-19 for ≤10 days prior to the day of randomization and ≥1 sign/symptom attributable to COVID-19 present at randomization
- •Requires medical care in the hospital for ongoing clinical manifestations of COVID-19 (not just for public health or quarantine purposes)
- •Has mild, moderate, or severe COVID-19
- •Is willing and able to take oral medication
- •Males agree to the following during the intervention period and for at least 90 days after the last dose of study intervention: Refrain from donating sperm; and either abstain from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception
- •Females are not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of child bearing potential (WOCBP); or is a WOCBP and using a contraceptive method that is highly effective (a low user dependency method OR a user dependent method in combination with barrier method), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) for 28 days from the start of study intervention; a WOCBP must have a negative highly sensitive pregnancy test (serum test is required) within 24 hours before the first dose of study intervention
排除标准
- •Has critical COVID-19 with any of the following: respiratory failure (including endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula (flow rates >20L/min with fraction of delivered oxygen ≥ 0.5), noninvasive positive pressure ventilation, or extracorporeal membrane oxygenation (ECMO))
- •Is on dialysis or has reduced estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2 by the Modification of Diet in Renal Disease (MDRD) equation
- •Has any of the following conditions: human immunodeficiency virus (HIV) with a recent viral load >50 copies/mL or cluster of differentiation 4 (CD4) <200 cell/mm^3; chemotherapy required within 6 weeks before randomization; a neutrophilic granulocyte absolute count <500/mm^3; autologous or allogeneic hematopoietic stem cell transplant recipient
- •Has history of Hepatitis B or Hepatitis C infection with any of the following: 1) cirrhosis 2) end-stage liver disease 3) hepatocellular carcinoma 4) aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times the upper limit of normal at screening
- •Has a history of acute pancreatitis within 3 months prior to randomization or a history of chronic pancreatitis
- •Is taking or is anticipated to require any prohibited therapies
- •Is unwilling to abstain from participating in another interventional clinical trial through Day 29 with an investigational compound or device, including those for COVID-19 therapeutics
- •Is anticipated to require transfer to a non-study hospital within 72 hours
- •Has a baseline heart rate of < 50 beats per minute at rest
- •Has a platelet count <100,000/μL or received a platelet transfusion in the 5 days prior to randomization
- •Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
- •Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments including but not limited to: participants who are not expected to survive longer than 48 hours after randomization or participants who are expected to require mechanical ventilation within 48 hours after randomization or participants with a recent history of mechanical ventilation or participants with conditions that could limit gastrointestinal absorption of capsule contents
研究组 & 干预措施
Part 1: Molnupiravir 200 mg
200 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
干预措施: Molnupiravir (Drug)
Part 1: Molnupiravir 800 mg
800 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
干预措施: Molnupiravir (Drug)
Part 1: Molnupiravir 400 mg
400 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
干预措施: Molnupiravir (Drug)
Part 1: Placebo
Placebo matching molnupiravir administered orally every 12 hours for 5 days (10 doses total)
干预措施: Placebo (Drug)
Part 2: Molnupiravir
Molnupiravir (dose to be selected) administered orally every 12 hours for 5 days (10 doses total)
干预措施: Molnupiravir (Drug)
Part 2: Placebo
Placebo matching molnupiravir administered orally every 12 hours for 5 days (10 doses total)
干预措施: Placebo (Drug)
结局指标
主要结局
Time-to-sustained Recovery
时间窗: Up to 29 days
The median time to sustained recovery is reported. Sustained recovery is defined as 1) the participant is alive and not hospitalized; or 2) the participant is alive and medically ready for discharge as determined by the investigator.
Number of Participants With an Adverse Event (AE)
时间窗: Up to 19 days (during treatment and 14-day follow-up)
The number of participants with at least 1 AE is presented. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Who Discontinued Study Intervention Due to an AE
时间窗: Up to 5 days
The number of participants discontinuing from study treatment due to an AE is presented. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
次要结局
- Odds of a More Favorable Response on Pulmonary Ordinal Outcome Score on Day 29(Day 29)
- Odds of a More Favorable Response on Pulmonary+ Ordinal Outcome Score on Day 3(Day 3)
- Odds of a More Favorable Response on Pulmonary+ Ordinal Outcome Score on Day 10(Day 10)
- Odds of a More Favorable Response on Pulmonary+ Ordinal Outcome Score on Day 15(Day 15)
- Odds of a More Favorable Response on Pulmonary+ Ordinal Outcome Score on Day 29(Day 29)
- Odds of a More Favorable Response in the Clinical Risk of Mortality Category From the National Early Warning Score(EOT (Day 5))
- Odds of a More Favorable Response on WHO 11-point Ordinal Outcomes Score on a Scale on Day 3(Day 3)
- Number of Participants With All-cause Mortality(Up to 29 days)
- Odds of a More Favorable Response on Pulmonary Ordinal Outcome Score on Day 3(Day 3)
- Odds of a More Favorable Response on Pulmonary Ordinal Outcome Score on End of Treatment (EOT [Day 5])(EOT (Day 5))
- Odds of a More Favorable Response on Pulmonary Ordinal Outcome Score on Day 10(Day 10)
- Odds of a More Favorable Response on Pulmonary Ordinal Outcome Score on Day 15(Day 15)
- Odds of a More Favorable Response on Pulmonary+ Ordinal Outcome Score on EOT (Day 5)(EOT (Day 5))
- Odds of a More Favorable Response on WHO 11-point Ordinal Outcomes Score on a Scale on EOT (Day 5)(EOT (Day 5))
- Odds of a More Favorable Response on WHO 11-point Ordinal Outcomes Score on a Scale on Day 10(Day 10)
- Odds of a More Favorable Response on WHO 11-point Ordinal Outcomes Score on a Scale on Day 15(Day 15)
- Odds of a More Favorable Response on WHO 11-point Ordinal Outcomes Score on a Scale on Day 29(Day 29)